Itch-free state in patients with atopic dermatitis treated with ruxolitinib cream: A pooled analysis from two randomized phase 3 studies
Authors: Andrew Blauvelt, Jacek C Szepietowski, Kim Papp, Eric L Simpson, Jonathan I Silverberg, Brian S Kim, Shawn G Kwatra, Michael E Kuligowski, May E Venturanza, Shaoceng Wei, Leon Kircik
Journal: Journal of the American Academy of Dermatology (2022)

To the Editor: Atopic dermatitis (AD), a highly pruritic, chronic inflammatory skin disease, affects patients' quality of life.1Langan S.M. Irvine A.D. Weidinger S. Atopic dermatitis.Lancet. 2020; 396: 345-360Abstract Full Text Full Text PDF PubMed Scopus (432) Google Scholar,2Silverberg J.I. Gelfand J.M. Margolis D.J. et al.Patient-burden and quality of life in atopic dermatitis in US adults: a population-based cross-sectional study.Ann Allergy Asthma Immunol. 2018; 121: 340-347Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar Previous reports identified itch as a significant symptom in adults and children with AD, with adults reporting it as the most burdensome symptom.2Silverberg J.I. Gelfand J.M. Margolis D.J. et al.Patient-burden and quality of life in atopic dermatitis in US adults: a population-based cross-sectional study.Ann Allergy Asthma Immunol. 2018; 121: 340-347Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar,3Drucker A.M. Wang A.R. Li W.Q. Sevetson E. Block J.K. Qureshi A.A. The burden of atopic dermatitis: summary of a report for the National Eczema Association.J Invest Dermatol. 2017; 137: 26-30Abstract Full Text Full Text PDF PubMed Scopus (331) Google Scholar In 2 identically designed phase 3 studies (TRuE-AD1/TRuE-AD2), ruxolitinib cream demonstrated anti-inflammatory and antipruritic activity and was well tolerated.4Papp K. Szepietowski J.C. Kircik L. et al.Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: results from two phase 3, randomized, double-blind studies.J Am Acad Dermatol. 2021; 85: 863-872Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar Here, we evaluated the achievement of an itch-free state using pooled data from these studies. Itch-free state was defined as patients (1) with baseline itch numerical rating scale (NRS) score >1 achieving a score of 0 or 1 (NRS 0/1; per patient reported worst itch level during each 24-hour period), (2) reporting no itch days in the preceding week per Patient-Oriented Eczema Measure question 1 (POEM Q1) among patients reporting ≥1 day of itch in the preceding week at baseline, and (3) achieving a SCORing Atopic Dermatitis itch score of 0 or 1 (SCORAD itch 0/1) among patients with baseline >1. All 1208 patients with baseline itch per NRS, SCORAD, or POEM Q1 were included, excluding 41 from 1 study site for quality issues. Patient proportions and number of days without itch per POEM Q1 were assessed using logistic regression. The log-rank test was used for between-group comparisons. A greater percentage of patients who applied ruxolitinib cream achieved an itch-free state versus vehicle. The difference versus vehicle in itch NRS 0/1 was statistically significant on Day 2 (≈36 hours after first application; Fig 1, A) and remained significant through Week 8 (Fig 1, B). The median time to achieve itch NRS 0/1 was 14.0 and 9.0 days for 0.75% and 1.5% ruxolitinib cream, respectively, versus not estimable for vehicle (Supplementary Fig 1, available via Mendeley at https://doi.org/10.17632/g65rf7psn5.1). In a multivariable proportional hazards regression model, age (<18 years [n = 198] vs ≥18 years [n = 877]) was the only factor significantly associated with faster itch response (median [95% confidence interval time to NRS 0/1: <18 years, 11.0 [8.0, 13.0] days; ≥18 years, 17.0 [14.0, 21.0] days; hazard ratio [95% confidence interval], 0.754 [0.630, 0.902]; P = .002) among factors examined (sex, race [White/Black/other], geographic region [North America/Europe], body surface area [<10%/≥10%], Eczema Area and Severity Index [≤7/>7], Investigator's Global Assessment [2/3]). A greater percentage of patients who applied ruxolitinib cream versus vehicle reported no days of itch per POEM Q1 (Supplementary Fig 2, available via Mendeley at https://doi.org/10.17632/g65rf7psn5.1), itch NRS 0/1 or POEM Q1 (Supplementary Fig 3, available via Mendeley at https://doi.org/10.17632/g65rf7psn5.1), or SCORAD itch 0/1 (Supplementary Fig 4, available via Mendeley at https://doi.org/10.17632/g65rf7psn5.1) at Week 2 through Week 8. Representative clinical images of patients achieving an itch-free state are displayed (Supplementary Fig 5, available via Mendeley at https://doi.org/10.17632/g65rf7psn5.1). Achievement of an itch-free state is critical for improving patients' quality of life and burden of illness, as itch can profoundly affect sleep, work productivity, and overall health.1Langan S.M. Irvine A.D. Weidinger S. Atopic dermatitis.Lancet. 2020; 396: 345-360Abstract Full Text Full Text PDF PubMed Scopus (432) Google Scholar,3Drucker A.M. Wang A.R. Li W.Q. Sevetson E. Block J.K. Qureshi A.A. The burden of atopic dermatitis: summary of a report for the National Eczema Association.J Invest Dermatol. 2017; 137: 26-30Abstract Full Text Full Text PDF PubMed Scopus (331) Google Scholar,5Hawro T. Przybyłowicz K. Spindler M. et al.The characteristics and impact of pruritus in adult dermatology patients: a prospective, cross-sectional study.J Am Acad Dermatol. 2021; 84: 691-700Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar In summary, a greater percentage of patients who applied ruxolitinib cream versus vehicle achieved an itch-free state (itch NRS 0/1) within approximately 36 hours and sustained it throughout the 8-week treatment period. These results demonstrate that ruxolitinib cream addresses an unmet need by rapidly improving itch, a chronic and burdensome symptom, in adults and adolescents with AD. AB has served as a speaker/received honoraria from AbbVie and UCB, served as a scientific adviser/received honoraria from AbbVie, Abcentra, Aligos, Almirall, Amgen, Anaptysbio, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, EcoR1, Eli Lilly and Company, Evommune, Forte, Galderma, HighlightII Pharma, Incyte Corporation, Janssen, Landos, LEO Pharma, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, UCB Pharma, Vibliome, and Xencor, and has acted as a clinical study investigator/received institutional clinical study funds from AbbVie, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, Galderma, Incyte, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB Pharma. JCS has served as an advisor for AbbVie, LEO Pharma, Novartis, Pierre Fabre, Menlo Therapeutics, and Trevi; has received speaker honoraria from AbbVie, Eli Lilly, Janssen-Cilag, LEO Pharma, Novartis, Sanofi Genzyme, and Sun Pharma; and has received clinical trial funding from AbbVie, Almirall, Amgen, Galapagos, Holm, Incyte, InflaRX, Janssen-Cilag, Menlo Therapeutics, Merck, Novartis, Pfizer, Regeneron, Trevi, and UCB. KP has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for AbbVie, Akros, Amgen, Anacor, Arcutis, Astellas, Bausch Health/Valeant, Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite, Celgene, Coherus, Dermira, Dow Pharmaceuticals, Eli Lilly, Galderma, Gilead, GlaxoSmithKline, Incyte, InflaRx, Janssen, Kyowa Hakko Kirin, LEO Pharma, Meiji Seika Pharma, Merck (MSD), Merck Serono, Mitsubishi Pharma, Moberg Pharma, Novartis, Pfizer, PRCL Research, Regeneron, Roche, Sanofi-Aventis/Genzyme, Sun Pharmaceuticals, Takeda, and UCB. ELS is an investigator for AbbVie, Eli Lilly, Galderma, Kyowa Hakko Kirin, LEO Pharma, Merck, Pfizer, and Regeneron and is a consultant with honorarium for AbbVie, Eli Lilly, Forte, Galderma, Incyte, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi Genzyme, and Valeant. JIS received honoraria for advisory board, speaker, and consultant services from AbbVie, Asana, Bluefin, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Glenmark, Incyte, Kiniksa, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Realm, Regeneron, and Sanofi and research grants for investigator services from Galderma and GlaxoSmithKline. BSK has served as a consultant to AbbVie, Almirall, Amagma, Cara Therapeutics, Daewoong, Incyte, OM Pharma, and Pfizer; has served on advisory boards for AstraZeneca, Boehringer Ingelheim, Cara Therapeutics, Celgene Corporation, Regeneron Pharmaceuticals, Sanofi Genzyme, and Trevi Therapeutics; is a shareholder in Locus Biosciences; and has a pending patent for JAK inhibitors in chronic itch. SGK is an advisory board member/consultant for AbbVie, Celldex Therapeutics, Galderma, Incyte, Johnson & Johnson, Kiniksa Pharmaceuticals, Novartis, Pfizer, Regeneron, and Sanofi and has served as an investigator for Galderma, Pfizer, and Sanofi. MEK and MEV were employees and shareholders of Incyte at the time of these studies. SW is an employee and shareholder of Incyte. LK has served as an investigator, consultant, or speaker for AbbVie, Amgen, Anaptys, Arcutis, Dermavant, Eli Lilly, Glenmark, Incyte, Kamedis, LEO Pharma, L'Oreal, Menlo Therapeutics, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun Pharma, and Taro. The authors thank the patients, investigators, and investigational sites whose participation made the studies possible. These studies were funded by Incyte Corporation. Writing assistance was provided by Vicky Kanta, PhD, an employee of ICON, and was funded by Incyte.